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Exploring the Cytoskeleton and Its Regulators: From Structure to Function

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 20 May 2025 | Viewed by 2312

Special Issue Editor


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Guest Editor
1. Department of Biochemistry, Dongguk University School of Medicine, Gyeongju 38066, Republic of Korea
2. Channelopathy Research Center (CRC), Dongguk University School of Medicine, Ilsan 10326, Republic of Korea
Interests: mechanotransduction; cytoskeleton remodeling; proliferation; differentiation; myogenesis; sarcopenia; insulin resistance; diabetes; metabolism; glucose metabolism; lipid metabolism; metabolic diseases; energy metabolism
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Special Issue Information

Dear Colleagues,

The cytoskeleton stands at the forefront of cellular organization, essential not only for maintaining structure but also for facilitating complex functions across cellular biology. It is a dynamic matrix that orchestrates numerous processes, such as mechanosensing, motility, adhesion, and signaling pathways. This matrix is intricately regulated by cytoskeleton-binding proteins (CBPs), which serve as crucial modulators of cytoskeletal behavior, interpreting mechanical stimuli into actionable biochemical signals that dictate cellular fate and behavior.

The cytoskeleton’s integral role in cell mechanics extends beyond static structural support; it actively participates in signaling networks that regulate cellular responses to environmental cues, impacting critical processes like proliferation, migration, differentiation, and survival. This dynamic involvement underscores the cytoskeleton’s pivotal role in understanding cellular behavior in physiological and pathological contexts.

Despite recent progress in the field, significant gaps remain in our understanding of how the cytoskeleton and CBPs coordinate and control the complex signaling pathways that influence cell behavior under different physiological and pathological states. This Special Issue seeks to bridge these gaps by gathering the latest research and comprehensive analyses that advance our understanding of the structural and functional roles of the cytoskeleton and its regulatory proteins.

This Special Issue aims to delve into the latest research and developments in cytoskeleton and CBP studies. We invite submissions of original research articles and comprehensive review papers that provide new insights into the structure, regulation, and function of the cytoskeleton and its associated proteins. Topics of interest include, but are not limited to, the following:

  • Mechanosensing and Mechanotransduction: Understanding how cells sense and respond to mechanical stimuli through cytoskeletal changes.
  • Cellular Motility and Migration: Investigating the mechanisms by which cytoskeletal components facilitate cell movement and tissue organization.
  • Signal Transduction Pathways: Exploring the biochemical pathways mediated by cytoskeletal elements and their impact on cellular decision-making.
  • Structural Analysis: Advanced imaging and molecular studies revealing the architecture of cytoskeletal networks.
  • The Cytoskeleton in Disease: Examining how alterations in cytoskeletal dynamics contribute to disease processes, including cancer, neurodegenerative disorders, and inflammatory responses.
  • Therapeutic Targets: Evaluating CBPs as potential therapeutic targets for modulating cellular behavior in disease treatment and prevention.

By gathering the latest findings in this field, we aim to provide a platform for the dissemination of knowledge that will foster further research and collaboration.

Prof. Dr. Wan Lee
Guest Editor

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Keywords

  • cytoskeleton
  • cytoskeleton-binding protein
  • cytoskeletal protein
  • cell signaling
  • mechanotransduction
  • cell proliferation
  • cell migration
  • cellular motility
  • cell differentiation
  • structural biology

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Published Papers (2 papers)

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Research

18 pages, 9775 KiB  
Article
Divergent Contribution of Cytoplasmic Actins to Nuclear Structure of Lung Cancer Cells
by Galina Shagieva, Vera Dugina, Anton Burakov, Yulia Levuschkina, Dmitry Kudlay, Sergei Boichuk, Natalia Khromova, Maria Vasileva and Pavel Kopnin
Int. J. Mol. Sci. 2024, 25(24), 13607; https://doi.org/10.3390/ijms252413607 - 19 Dec 2024
Viewed by 962
Abstract
A growing body of evidence suggests that actin plays a role in nuclear architecture, genome organisation, and regulation. Our study of human lung adenocarcinoma cells demonstrates that the equilibrium between actin isoforms affects the composition of the nuclear lamina, which in turn influences [...] Read more.
A growing body of evidence suggests that actin plays a role in nuclear architecture, genome organisation, and regulation. Our study of human lung adenocarcinoma cells demonstrates that the equilibrium between actin isoforms affects the composition of the nuclear lamina, which in turn influences nuclear stiffness and cellular behaviour. The downregulation of β-actin resulted in an increase in nuclear area, accompanied by a decrease in A-type lamins and an enhancement in lamin B2. In contrast, the suppression of γ-actin led to upregulation of the lamin A/B ratio through an increase in A-type lamins. Histone H3 post-translational modifications display distinct patterns in response to decreased actin isoform expression. The level of dimethylated H3K9me2 declined while acetylated H3K9ac increased in β-actin-depleted A549 cells. In contrast, the inhibition of γ-actin expression resulted in a reduction in H3K9ac. Based on our observations, we propose that β-actin plays a role in chromatin compaction and deactivation, and is involved in the elevation of nuclear stiffness through the control of the lamins ratio. The non-muscle γ-actin is presumably responsible for chromatin decondensation and activation. The identification of novel functions for actin isoforms offers insights into the mechanisms through which they influence cell fate during development and cancer progression. Full article
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16 pages, 3701 KiB  
Article
Essential Role of Cortactin in Myogenic Differentiation: Regulating Actin Dynamics and Myocardin-Related Transcription Factor A-Serum Response Factor (MRTFA-SRF) Signaling
by Quoc Kiet Ly, Mai Thi Nguyen, Thanh Huu Phan Ngo and Wan Lee
Int. J. Mol. Sci. 2024, 25(24), 13564; https://doi.org/10.3390/ijms252413564 - 18 Dec 2024
Viewed by 788
Abstract
Cortactin (CTTN) is an actin-binding protein regulating actin polymerization and stabilization, which are vital processes for maintaining skeletal muscle homeostasis. Despite the established function of CTTN in actin cytoskeletal dynamics, its role in the myogenic differentiation of progenitor cells remains largely unexplored. In [...] Read more.
Cortactin (CTTN) is an actin-binding protein regulating actin polymerization and stabilization, which are vital processes for maintaining skeletal muscle homeostasis. Despite the established function of CTTN in actin cytoskeletal dynamics, its role in the myogenic differentiation of progenitor cells remains largely unexplored. In this study, we investigated the role of CTTN in the myogenic differentiation of C2C12 myoblasts by analyzing its effects on actin cytoskeletal remodeling, myocardin-related transcription factor A (MRTFA) nuclear translocation, serum response factor (SRF) activation, expression of myogenic transcription factors, and myotube formation. CTTN expression declined during myogenic differentiation, paralleling the reduction in MyoD, suggesting a potential role in the early stages of myogenesis. We also found that CTTN knockdown in C2C12 myoblasts reduced filamentous actin, enhanced globular actin levels, and inhibited the nuclear translocation of MRTFA, resulting in suppressed SRF activity. This led to the subsequent downregulation of myogenic regulatory factors, such as MyoD and MyoG. Furthermore, CTTN knockdown reduced the nuclear localization of YAP1, a mechanosensitive transcription factor, further supporting its regulatory roles in cell cycle and proliferation. Consequently, CTTN depletion impeded proliferation, differentiation, and myotube formation in C2C12 myoblasts, highlighting its dual role in the coordination of cell cycle regulation and myogenic differentiation of progenitor cells during myogenesis. This study identifies CTTN as an essential regulator of myogenic differentiation via affecting the actin remodeling-MRTFA-SRF signaling axis and cell proliferation. Full article
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